Syzygium australe (J.C.Wendl. ex Link) B.Hyland and Syzygium luehmannii (F.Meell.) L.A.S. Johnson Extracts Inhibit Methicillin-Resistant Staphylococcus aureus and ESBL Escherichia coli and Klebsiella pneumoniae

Background: Recent increases in antibiotic-resistant bacteria infections has focussed researcher’s attention on alternative therapies, including traditional plant-based medicines. The rapid development β-lactam resistant bacterial strains with resistance to later generation antibiotics including methicillin is particularly worrisome due to the reliance of medical science on β-lactam antibiotics to treat many common infections. Materials and Methods: The antibacterial activity of Syzygium australe and Syzygium luehmannii leaf and fruit extracts towards β-lactam resistant and sensitive bacterial strains was investigated and quantified by disc diffusion assays and broth microdilution assays. Combinational effects were evaluated in broth microdilution assays by determining ΣFIC values. Toxicity was assessed using Artemia nauplii cytotoxicity assays and therapeutic indices were calculated. Results: Most of the S. australe and S. luehmannii leaf and fruit extracts displayed noteworthy growth inhibitory activity against all of the bacteria tested, including MRSA and ESBL E. coli and K. pneumonia strains. The S. australe fruit ethyl acetate extract had particularly good antibacterial activity, with MIC values generally between 350 and 710 μg/mL. Notably, this extract was a better inhibitor of the ESBL E. coli strain than against the antibiotic-sensitive strain. The methanolic and aqueous S. australe fruit extracts were also generally good bacterial growth inhibitors (MIC values <1000 μg/mL), although they were less effective against both S. aureus strains. Several combinations of the extracts and either ciprofloxacin or gentamicin had potentiated activity (either synergistic or additive effects). All of the extracts were either nontoxic or of low toxicity in the Artemia nauplii lethality assay and the calculated therapeutic indexes (TIs) of the majority of the extracts indicated their safety for use as antibiotic chemotherapies. Conclusion: Our study demonstrated that S. australe (and to a lesser extent, S. luehmannii) leaf and fruit extracts have potential to treat antibiotic-resistant bacterial infections and potentiate the activity of ciprofloxacin and gentamicin. The low toxicity and relatively high therapeutic indexes (TIs) of many of the extracts indicated their safety for use as antibiotic chemotherapies. Further phytochemical and mechanistic studies of these extracts are warranted.